Caffeoylquinic acid derivatives isolated from <i>Tussilago farfara</i> L. as potential anti-leishmanial agents; <i>in vitro</i> and <i>in silico</i> studies

Leishmaniasis affects millions of people in tropical and subtropical regions. Currently, only a few medications are available for its treatment, many of which cause adverse effects. Therefore, the development of effective, and safer drugs is urgently needed. <i>Leishmania major</i> Pteridine reductase-1 (<i>Lm</i>PTR-1) is a vital enzyme for parasite survival, and thus serves as a valid drug target. Our investigation on the ethanolic extract of <i>Tussilago farfara</i> L. resulted in the isolation of twenty known phenolic compounds <b>1</b>-<b>20</b>. Among them, vanillic acid (<b>1</b>), 1<i>S</i>,3<i>R</i>,4<i>R</i>,5<i>R</i>)<b>-</b>3,5-di-<i>O</i>-caffeoylquinic acid (<b>14</b>), and 3,4,5-tri-<i>O</i>-caffeoylquinic acid methyl ester (<b>20</b>) are first time reported here. Compounds (1<i>S</i>,3<i>R</i>,4<i>S</i>,5<i>R</i>)-3,5-di-<i>O</i>-caffeoylquinic acid (<b>15</b>), 3,4-di-<i>O</i>-caffeoylquinic acid (<b>16</b>), 4,5-di-<i>O</i>-caffeoylquinic acid (<b>17</b>), and 3,4-di-<i>O</i>-caffeoylquinic acid methyl ester (<b>18</b>) exhibited <i>Lm</i>PTR-1 inhibition with IC₅₀ between 81.9-189.7 μΜ. <i>In silico</i> studies further revealed strong interactions between compounds <b>15</b>-<b>18</b>, and <i>Lm</i>PTR-1 enzyme. In summary, quinic acid derivatives, containing caffeoyl moieties can serve as potential as anti-leishmanial agents.